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Epidemiology
Abstracts of selected papers
BACKGROUND: Investigations on cause of death may provide valuable information about life expectancy and on conditions of terminal dementia care, which perhaps can be ameliorated. METHODS: The autopsy reports were studied on all patients (n = 524; 55.3% females; median age 80 years) with a clinically and neuropathologically diagnosed dementia disorder who underwent a complete autopsy at the University Hospital in Lund, Sweden, during 1974-2004. RESULTS: The two most common causes of death were bronchopneumonia (38.4%) and ischaemic heart disease (23.1%), whilst neoplastic diseases were uncommon (3.8%). In a general population of elderly studied for comparison, bronchopneumonia accounted for 2.8%, ischaemic heart disease for 22.0%, and neoplasm for 21.3% of the deaths. Amongst the demented patients, circulatory and respiratory system diseases were the causes of death in 23.2% and 55.5% of the Alzheimer patients, respectively, whilst the corresponding figures were 54.8% and 33.1% for the patients with vascular dementia. CONCLUSIONS: In patients with dementia, pneumonia as the immediate cause of death may reflect a terminal stage in which patient care and feeding is difficult to manage well. Knowledge about what actually causes death is of value in the terminal care of patients with dementia disorders.
OBJECTIVE: To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI). METHOD: We followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria. RESULTS: Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk [RR] = 1.8 [1.2 to 2.7] per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 [1.0 to 3.6] per symptom). CONCLUSIONS: The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.
The authors determined the prevalence of dementia in 338 (response rate 65%) 95-year-old persons, living in Göteborg, Sweden, and compared the result with a previously examined population sample of 85 year olds. The prevalence of dementia according to the Diagnostic and Statistical Manual of Mental Disorders (3rd rev. ed) was higher in women (55%) than in men (37%) at age 95, and the proportion of mild dementia and vascular dementia was lower in 95 than in 85 year olds.
In this study, the authors evaluated whether the association between low educational level and increased risk of Alzheimer's disease (AD) and dementia may be explained by occupation-based socioeconomic status (SES). A cohort of 931 nondemented subjects aged > or = 75 years from the Kungsholmen Project, Stockholm, Sweden, was followed for 3 years between 1987 and 1993. A total of 101 incident cases of dementia, 76 involving AD, were detected. Less-educated subjects had an adjusted relative risk of developing AD of 3.4 (95% confidence interval: 2.0, 6.0), and subjects with lower SES had an adjusted relative risk of 1.6 (95% confidence interval: 1.0, 2.5). When both education and SES were introduced into the same model, only education remained significantly associated with AD. Combinations of low education with low or high SES were associated with similar increased risks of AD, but well-educated subjects with low SES were not at high risk. Low SES at 20 years of age, even when SES was high at age 40 or 60 years, was associated with increased risk; however, this increase disappeared when education was entered into the model. In conclusion, the association between low education and increased AD risk was not mediated by adult SES or socioeconomic mobility. This suggests that early life factors may be relevant.
BACKGROUND AND PURPOSE: Elevated blood pressure has been found to increase the risk of dementia, including Alzheimer disease. We sought to investigate whether pulse pressure was predictive of Alzheimer disease and dementia. METHODS: A community-based, dementia-free cohort (n=1270) aged > or =75 years was clinically examined twice over 6 years to detect incident dementia with the use of the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Cox proportional hazards models were used to analyze pulse pressure in association with incident Alzheimer disease and dementia after adjustment for several potential confounders, including systolic pressure and diastolic pressure. RESULTS: During the 5464.6 person-years (median, 4.7 years) of follow-up, 339 subjects developed dementia, including 256 Alzheimer disease cases. Pulse pressure as a continuous variable was not statistically related to the risk of Alzheimer disease and dementia. In the categorical analysis, however, in comparison with median tertile of pulse pressure (70 to 84 mm Hg), subjects with higher pulse pressure had adjusted relative risks (95% CI) of 1.4 (1.0 to 2.0; P=0.04) for Alzheimer disease and 1.3 (0.9 to 1.7) for dementia. The corresponding figures related to lower pulse pressure were 1.7 (1.2 to 2.3) for Alzheimer disease and 1.4 (1.0 to 1.9; P=0.03) for dementia. This association was particularly pronounced among women. CONCLUSIONS: Higher pulse pressure is associated with increased risk for Alzheimer disease and dementia in old adults, which is probably due to artery stiffness and severe atherosclerosis. Poor cerebral perfusion related to decreased pulse pressure may explain the association between lower pulse pressure and increased dementia risk.
BACKGROUND: Some studies suggest that manual work is associated with dementia. This study is aimed at identifying the specific occupational categories that may be related to dementia. METHODS: A cohort of 913 non-demented subjects aged 75 + years was longitudinally examined twice over 6 years to detect incident dementia using the DSM-III-R diagnostic criteria. The lifetime longest occupations of all subjects were divided into different categories according to the occupation-based classification system. Data were analyzed with Cox models. RESULTS: During the follow-up period, 260 subjects were diagnosed with dementia (197 with Alzheimer's disease). Manual work was associated with an increased risk of dementia, and the association was dependent on educational level. Compared with non-manual work, manual work involving goods production had a multi-adjusted relative risk (95% CI) of 1.6 (1.0-2.5, P = 0.046) for Alzheimer's disease and 1.4 (0.9-2.1) for dementia. CONCLUSIONS: An association between goods production, manual work and Alzheimer's disease found in this study suggests that factors in the mid-twentieth century goods production environment may be involved in the development of Alzheimer's disease.
BACKGROUND: The relationship between education and Alzheimer disease (AD) or dementia has been widely examined and the evidence obtained is mixed. Several hypotheses have been proposed to explain the observed association between them. OBJECTIVE: To further understand the relationship between education and incidence of clinically diagnosed AD or dementia. SUBJECTS AND METHODS: A community-based, dementia-free cohort of 1296 aged 75 years and older was followed up to detect incident AD or dementia cases using Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria. The vital status of all subjects who underwent the clinical examination at follow-up (n = 983) was ascertained for 5 years further. Data were analyzed with Cox proportional hazards model after adjustment for main potential confounders. RESULTS: Over an average (SD) of 2.8 (1.0) years of follow-up, 147 subjects were diagnosed as having dementia (109 subjects as having AD). Among those who were clinically examined at follow-up, 88 died with dementia (68 died with AD) within 5 years. Subjects with a low level of education (<8 vs > or =8 years) had a relative risk of 2.6 (95% confidence interval, 1.5-4.4) for AD and 1.7 (95% confidence interval, 1.1-2.6) for dementia. A low educational level was significantly related to all-cause mortality (relative risk, 1.3; 95% confidence interval, 1.0-1.7; P<.05), but not to the mortality of subjects with AD (relative risk, 1.1; 95% confidence interval, 0.5-2.2) or dementia (relative risk, 0.9; 95% confidence interval, 0.5-1.5). CONCLUSIONS: A low level of education is related to an increased incidence of clinical AD or dementia, but not to the mortality of subjects with AD or dementia. These findings can be accounted for by the "cognitive reserve" hypothesis. Alternatively, the observed association between educational level and incidence of AD or dementia may partly reflect detection bias, by which subjects with a low level of education tend to be clinically diagnosed at an earlier point in time.
OBJECTIVE: To investigate the survival rate in very elderly individuals in relation to Alzheimer disease, vascular dementia, and other mental and physical disorders. DESIGN: A 7-year longitudinal survey. SETTING: Community and institutions in Gothenburg, Sweden. PARTICIPANTS: A representative sample of 494 people aged 85 years. MAIN OUTCOME MEASURES: Results of neuropsychiatric and physical examinations, key informant interview, and computed tomographic scan of the head. Information on mortality was obtained from the parish office. RESULTS: The 7-year survival rate was higher in women (34.5%) than in men (20.3%). Alzheimer disease and vascular dementia predicted 30.7% of deaths in men and 49.7% of deaths in women according to a calculation of population attributable risk (PAR). A regression analysis showed that mortality in men was predicted by the presence of chronic obstructive lung disease (PAR, 18.8), Alzheimer disease (PAR, 16.0), vascular dementia (PAR, 14.7), cancer of the gastrointestinal tract (PAR, 10.2), and skin cancer (PAR, 6.2), and in women by vascular dementia (PAR, 29.4), Alzheimer disease (PAR, 20.3), cerebrovascular disorder (PAR, 12.1), congestive heart failure (PAR, 8.5), hypertension (PAR, 8.0), myocardial infarction (PAR, 6.5), and cancer of the gastrointestinal tract (PAR, 4.3). Life expectancy decreased with severity of dementia, although survival time in individuals with mild Alzheimer disease was not different from that in individuals without dementia. CONCLUSIONS: In extreme old age, Alzheimer disease and vascular dementia influence the mortality rate considerably. However, mild Alzheimer disease does not influence longevity, at least not during the first 7 years. These findings have important public health implications.
OBJECTIVE: To determine the incidence of different types of dementia in the very old, and to explore the relation with age and gender. DESIGN: A dementia-free cohort was followed for an average of three years in Stockholm, Sweden. At the end of the follow-up, the subjects were interviewed by nurses, clinically examined by physicians, and cognitively assessed by psychologists. Deceased cohort members were studied using death certificates, hospital clinical records, and discharge diagnoses. Dementia diagnoses were made according to the DSM-III-R criteria independently by two physicians. PARTICIPANTS: The cohort consisted of 1,473 subjects (75+ years old), of which 987 were clinically examined at follow-up, 314 died before the examination, and 172 refused to participate. RESULTS: During the follow-up, 148 subjects developed dementia. In the age-group 75 to 79, the incidence rates for dementia were 19.6 for women and 12.4 for men per 1,000 person-years, whereas for 90+ year-old subjects the corresponding figures were 86.7 and 15.0 per 1,000 person-years. A similar pattern of distribution by age and gender was seen for Alzheimer's disease. In each age stratum, the incidence rates of dementia and Alzheimer's disease were higher for women than for men. The age-adjusted odds ratio for women was 1.9 for dementia and 3.1 for Alzheimer's disease. CONCLUSIONS: (1) The incidence of dementia increases with age, even in the oldest age groups; (2) women have a higher risk of developing dementia than men, especially at very old ages; (3) this pattern is mainly due to the age and gender distribution of Alzheimer's disease, rather than vascular dementia.
OBJECTIVE: To investigate the incidence of Alzheimer's disease, vascular dementia and other dementias in a population between 85 and 88 years of age. DESIGN: Prospective cohort study. Longitudinal population study of the very old. SETTING: Systematic sample of a birth cohort living in the community or in institutions in the city of Gothenburg, Sweden. PARTICIPANTS: A representative population sample of nondemented 85-year-old residents (n = 347). MEASUREMENTS: The study included neuropsychiatric, neuropsychological, and physical examinations, key informant interviews, comprehensive laboratory tests, electrocardiography, chest radiography and computed tomography (CT-scan) of the head. Information on subjects lost during the follow-up period as a result of death or refusal was traced in medical records. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (3rd Edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to criteria proposed by Erkinjuntti. RESULTS: Sufficient information was obtained about 92% of the subjects at risk. Sixty-three subjects (18.2%) became demented between ages 85 and 88, giving an incidence of 90.1/1000/year (61.3/1000/year for men and 102.7/1000/ year for women; P = .085). The incidence of Alzheimer's disease was 36.3/1000/year, vascular dementia 39.0/1000/ year (P = 1.000), and that of other dementias 9.1/1000/year. CONCLUSION: This study shows that almost one-tenth of nondemented persons between the ages of 85 and 88 become demented each year, emphasizing the magnitude of the dementia problem in the very old, the fastest growing segment of western populations.
Our current knowledge of risk factors for Alzheimer's disease is limited and primarily addresses early-onset disease. This study aimed to determine the risk factors for late-onset Alzheimer's disease using a case-control approach. Ninety-eight cases and 216 controls were gathered from an ongoing population survey on aging and dementia in Stockholm (the Kungsholmen Project). We found a high relative risk (3.2; 95% confidence interval, 1.8-5.7) with the presence of at least one first-degree relative affected by dementia. Among all the other risk factors, alcohol abuse (relative risk, 4.4; 95% confidence interval, 1.4-13.8) and manual work (relative risk for men of 5.3; 95% confidence interval, 1.1-25.5) emerged as positively associated. No clear association was found with a family history of Parkinson disease, advanced parental age at index delivery, season of birth, or previous head trauma. In conclusion, our data suggest that the main risk factor for late-onset Alzheimer's disease is a family history of dementia, as has been previously reported for early-onset disease. Moreover, alcohol abuse and occupational exposure might play a specific role for this form of the disease.
BACKGROUND. The aim of this study was to investigate the causes, severity, and prevalence of dementia in a representative sample of 494 85-year-olds living in Gothenburg, Sweden. METHODS. The study included a psychiatric interview, neuropsychological and physical examinations, comprehensive laboratory tests, electrocardiography, chest radiography, computed tomography (CT) of the head, and analysis of cerebrospinal fluid. A person close to each subject was also interviewed. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to recently proposed criteria that incorporate information from CT scanning and the patient's neurologic history. RESULTS. The prevalence of dementia was 29.8 percent (147 subjects). The condition was mild in 8.3 percent, moderate in 10.3 percent, and severe in 11.1 percent. There were no significant sex-related differences in prevalence or severity. Of the subjects with dementia, 43.5 percent had Alzheimer's disease, 46.9 percent had vascular dementia (multi-infarct dementia in 34.6 percent, dementia related to cerebral hypoperfusion in 4.1 percent, and mixed dementia in 8.2 percent), and 9.5 percent had dementia due to other causes. The three-year mortality rate was 23.1 percent in the subjects without dementia, 42.2 percent in the patients with Alzheimer's disease, and 66.7 percent in the patients with vascular dementia. Infarcts detected by CT scanning were significantly more common in the subjects with dementia than in those without it (27.9 percent vs. 12.6 percent). CONCLUSIONS. Dementia was present in nearly a third of unselected 85-year-olds in Sweden. Almost half these subjects appeared to have vascular dementia, which may currently be more amenable to prevention or treatment than Alzheimer's disease.
The incidences of senile dementia of Alzheimer type (SDAT) and multi-infarction dementia (MID) were studied in a total Swedish population, the Lundby project. The study is prospective and covers a 25-year period. The incidence rates per year of contracting SDAT or MID and the probability in each 10-year age interval of contracting dementia in the elderly were calculated, as well as the cumulative risk up to a certain age. The lifetime risk of contracting SDAT was for men 25.5% and for women 31.9%. The corresponding figures for MID were 29.8 and 25.1%.
In spite of the great impact of senile dementia of the Alzheimer type (SDAT) on society, far too little is known about its epidemiology. In this study of a total, normal population from a geographically delimited area in Sweden, Lundby, 2612 persons were examined in 1957 by one psychiatrist (Hagnell). In 1972 the same population was reexamined irrespective of domicile. The incidence and risk of contracting SDAT during the 15 years were calculated. No cases of SDAT were diagnosed before the age of 60 years. The lifetime risk was for men 25.7% and for women 26.2%. When only the very severely impaired were taken into account, the figures were 14.5% in men and 14.6% in women.
Economics
Abstracts of selected papers
OBJECTIVES: The purpose of this study was to compare resource use and costs in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) and to assess determinants of costs of care in DLB. METHOD: Thirty-four patients with DLB were included in a cross-sectional study. The patients were matched with respect to age, gender and Mini Mental State Examination (MMSE) score to 34 patients with AD. Both groups were examined using Resource Utilisation in Dementia (RUD Lite), MMSE and the Neuropsychiatric inventory (NPI). The DLB patients were additionally examined using the Disability Assessment for Dementia Scale (DAD). RESULTS: Costs of care in patients suffering from DLB was on average 348,000 SEK (37,500 euro) per year compared to 169,000 SEK (18,200 euro) in the AD group (p < 0.001). Within the DLB group, care costs correlated significantly (r(c) = 2.77, p < 0.001) with dependency in instrumental activities of daily living measured with DAD, whereas MMSE and NPI were not significantly correlated to resource use in the DLB group. CONCLUSIONS: DLB patients use more resources, and are more costly than AD patients. Dependency in instrumental activities of daily living is strongly correlated to resource use in DLB patients.
BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, is a major cause of disability and care burden in the elderly. This study aims to estimate the costs of formal and informal care and identity determinants of care costs. MATERIALS AND METHODS: Two hundred and seventy-two (AD) patients and their caregivers were recruited among patients attending regular visits at six memory clinic in Sweden, Denmark, Norway and Finland. Patients with a diagnosis of AD and with an identifiable primary caregiver were eligible for inclusion. Data was collected by questionnaires at baseline, and at scheduled follow-up visits after 6 months and again after 12 months. Cognitive function was assessed with the Mini Mental State Examination (MMSE) and behavioural disturbances were measured using a brief version of the neuropsychiatric inventory (NPI). RESULTS: Total annual costs were on average 172,000 SEK, ranging from 60,700 SEK in mild dementia to 375,000 SEK in severe dementia. Costs for community care (special accommodation, home help, etc.) constituted about half of total costs of care and increase sharply with increasing cognitive impairment. Informal care costs, valued at the opportunity cost of the caregiver's time, make up about a third of total costs and also increased significantly with disease severity. Medical care costs (inpatient care, outpatient care, pharmaceuticals), on the other hand, were not significantly related to disease severity. Regression analysis confirmed a strong association between costs and cognitive function, between patients as well as within patients over time. There was also a significant influence on costs from behavioural disturbances. Sensitivity analysis showed that the method chosen to value informal care can have considerable impact on results. CONCLUSIONS: Costs of care in patient with AD are high and related to dementia severity as well as presence of behavioural disturbances. The cost estimates presented have implications for future economic evaluation of treatments for Alzheimer's disease.
BACKGROUND: Alzheimer's disease entails enormous costs for society and impairs quality of life for patients and caregivers. OBJECTIVE: This study estimated the cost-effectiveness of memantine in the treatment of patients with moderately severe to severe cognitive impairment from Alzheimer's disease in Sweden. METHODS: The study was based on published data from several sources, including a randomized controlled trial of memantine versus placebo and a longitudinal observational study of Alzheimer's disease patients in Sweden. Costs were estimated from the public payer's perspective, including direct costs but excluding costs of informal care, and resource utilization data were taken from the observational study. Cost-effectiveness was quantified as quality-adjusted life-years (QALYs) gained from treatment with the use of previously published utility weights. A Markov simulation model was constructed, incorporating the effect of treatment on cognitive function, physical dependence related to activities of daily living, and institutionalization. Costs and effects for treated and untreated patients were estimated for 5 years (10 cycles). In the base-case analysis, treatment costs were added for 2 years, but the effect on transition probabilities was applied only for the first year of treatment. RESULTS: Compared with no treatment, memantine treatment was predicted to be associated with lower costs of care, longer time to dependence and institutionalization, and gains in QALYs. Treatment was estimated to decrease formal care costs by 123,600 Swedish kronor (SEK) and, after taking into account the cost of memantine, to lead to net cost savings of 100,528 SEK per patient. Treated patients gained 0.148 QALY over the 5-year simulation. CONCLUSIONS: From a public payer's perspective, the observed effect of memantine on cognitive and physical function is predicted to translate into economic benefits that offset the added treatment cost. Treatment is also predicted to delay institutionalization, improve independence, and increase QALYs.
Alzheimer disease and related disorders associations
Edité par Aldo Campana,